Sequencing of the smallest Apicomplexan genome from the human pathogen Babesia microti†

Cornillot, Emmanuel; Hadj-Kaddour, Kamel; Dassouli, Amina; Noël, Benjamin; Ranwez, Vincent; Vacherie, Benoît; Augagneur, Yoann; Brès, Virginie; Duclos, Antoine; Randazzo, Sylvie; Carcy, B.; Debierre‐Grockiego, Françoise; Delbecq, Stéphane; Moubri-Ménage, Karina; Shams‐Eldin, Hosam; Usmani‐Brown, Sahar; Bringaud, Frédéric; Wincker, Patrick; Vivarès, Christian P.; Schwarz, Ralph Τ.; Schetters, Theo; Krause, Peter J.; Gorenflot, A.; Berry, Vincent; Barbe, Valérie; Mamoun, Choukri Ben

doi:10.1093/nar/gks700

Cited by 185 publications

(263 citation statements)

References 76 publications

(67 reference statements)

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“…Analysis of the pattern of hybridization revealed that the gene encoding BmAMA1 was present as a single-copy gene (data not shown). This result is further corroborated by the recently published B. microti genome sequence (36), which suggests the presence of a single copy of the BmAMA1 gene on chromosome 3. (Fig.…”

Section: Resultssupporting

confidence: 79%

“…The AMA1 sequence derived from gDNA of B. microti has a small 23-nucleotide intron compared to the sequence derived from cDNA. The presence of short introns is a common occurrence in B. microti; genome sequencing has revealed that about 70% of all B. microti genes contain introns of 20 to 25 bp in length (36). We found that the BmAMA1 gene sequence was highly conserved among B. microti parasites from Nantucket Island, MA.…”

Section: Discussionmentioning

confidence: 77%

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Expression, Purification, and Biological Characterization of Babesia microti Apical Membrane Antigen 1

et al. 2015

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eThe intraerythrocytic apicomplexan Babesia microti, the primary causative agent of human babesiosis, is a major public health concern in the United States and elsewhere. Apicomplexans utilize a multiprotein complex that includes a type I membrane protein called apical membrane antigen 1 (AMA1) to invade host cells. We have isolated the full-length B. microti AMA1 (BmAMA1) gene and determined its nucleotide sequence, as well as the amino acid sequence of the AMA1 protein. This protein contains an N-terminal signal sequence, an extracellular region, a transmembrane region, and a short conserved cytoplasmic tail. It shows the same domain organization as the AMA1 orthologs from piroplasm, coccidian, and haemosporidian apicomplexans but differs from all other currently known piroplasmida, including other Babesia and Theileria species, in lacking two conserved cysteines in highly variable domain III of the extracellular region. Minimal polymorphism was detected in BmAMA1 gene sequences of parasite isolates from six babesiosis patients from Nantucket. Immunofluorescence microscopy studies showed that BmAMA1 is localized on the cell surface and cytoplasm near the apical end of the parasite. Native BmAMA1 from parasite lysate and refolded recombinant BmAMA1 (rBmAMA1) expressed in Escherichia coli reacted with a mouse anti-BmAMA1 antibody using Western blotting. In vitro binding studies showed that both native BmAMA1 and rBmAMA1 bind to human red blood cells (RBCs). This binding is trypsin and chymotrypsin treatment sensitive but neuraminidase independent. Incubation of B. microti parasites in human RBCs with a mouse anti-BmAMA1 antibody inhibited parasite growth by 80% in a 24-h assay. Based on its antigenically conserved nature and potential role in RBC invasion, BmAMA1 should be evaluated as a vaccine candidate.

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Section: Resultssupporting

confidence: 79%

Section: Discussionmentioning

confidence: 77%

Expression, Purification, and Biological Characterization of Babesia microti Apical Membrane Antigen 1

et al. 2015

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“…The Plasmodium and Babesia genera are relatively closely related among the apicomplexans (1) (last common ancestor, ϳ55 million years ago [2]) ( Fig. 1A) and share similar features in their biology, including mechanisms for host cell invasion and metabolism (3)(4)(5)(6). Both Plasmodium and Babesia spp.…”

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confidence: 99%

Extensive Shared Chemosensitivity between Malaria and Babesiosis Blood-Stage Parasites

Paul

Moreira

Elsworth

et al. 2016

Antimicrob Agents Chemother

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The apicomplexan parasites that cause malaria and babesiosis invade and proliferate within erythrocytes. To assess the potential for common antiparasitic treatments, we measured the sensitivities of multiple species of Plasmodium and Babesia parasites to the chemically diverse collection of antimalarial compounds in the Malaria Box library. We observed that these parasites share sensitivities to a large fraction of the same inhibitors and we identified compounds with strong babesiacidal activity.T he apicomplexan phylum of eukaryotic microbial parasites is important in human and veterinary medicine. Apicomplexans cause malaria (Plasmodium spp.), babesiosis (Babesia spp.), toxoplasmosis (Toxoplasma gondii), and cryptosporidiosis (Cryptosporidium spp.), among other diseases. The Plasmodium and Babesia genera are relatively closely related among the apicomplexans (1) (last common ancestor, ϳ55 million years ago [2]) ( Fig. 1A) and share similar features in their biology, including mechanisms for host cell invasion and metabolism (3-6). Both Plasmodium and Babesia spp. are pathogenic during the stage of infection when parasites colonize host erythrocytes. Historically, drug development has focused more strongly on inhibitors for Plasmodium sp. parasites (7). Researchers have found that some antimalarial drugs also reduce proliferation of Babesia sp. parasites in erythrocytes as well (8, 9). The antimalarial atovaquone, a ubiquinone analog, is the preferred clinical treatment for human babesiosis in combination with azithromycin (10) and is used also in veterinary practice for babesiosis in dogs (11).A renewed focus on malaria eradication has led to the identification of an unprecedented number of bioactive compounds that block proliferation of Plasmodium falciparum in erythrocytes (12). In 2011, the nonprofit group Medicines for Malaria Venture (MMV) made available to the research community the Malaria Box, a collection of 400 chemically diverse, previously uncharacterized blood-stage antimalarials (13). Researchers have screened the antiparasitic activities of the Malaria Box compounds in nonerythrocytic host cells for the apicomplexans T. gondii, Cryptosporidium parvum, and Theileria annulata and identified a limited number of inhibitors (Ͻ3% of the library) active against each of these species (14-16). Here, we measured the susceptibilities of multiple blood-stage Plasmodium and Babesia parasite species to the Malaria Box compounds and found that erythrocyte-specific apicomplexans share considerable chemical sensitivities during the clinically relevant stages of parasitic infection.To determine the species-specific action of the Malaria Box compounds, we measured the chemical susceptibility of Plasmodium knowlesi in parallel with the reference species P. falciparum (13) (see Dataset S1 in the supplemental material). Endemic to macaque monkeys in southeast Asia and an emerging zoonosis in humans, P. knowlesi is distinguished from P. falciparum by its shorter blood-stage cell cycle and reduced rate of parasite mult...

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“…These analysis shows that this species does not belong to none of the established genera -Babesia and Theileria -but to a separate genus [12].…”

Section: Typical Fi Nal Hosts and Vectors Of B Microti In Europe Arementioning

confidence: 86%

Babesia Microti – Known and Unknown Protists

Albertyńska¹,

Rupik²,

Hermyt³

et al. 2017

Glob J Zool

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B. microti is known as the main etiological agent of human babesiosis and there are some case studies for that disease, highlighting the fact that this is an important "emerging tick-borne disease". However a lot of information about this protist is unclear.The reactions in the liver are noticeable already after the fi rst three weeks of infection. This therefore provides the basis for discussion of the effect of B. microti contact with hepatocytes in vitro and in vivo. This issue is an essential objective of our study.The effect of B. microti on the liver as an organ and the individual hepatocytes is evident. This may be an indirect impact, through the various factors of metabolic pathways. Ultrastructural studies of breeding co-culture of hepatocytes and B. microti has shown, however, that piroplasms B. microti are adhering to the outer surface of the hepatocytes. This contact is associated with destructive changes in hepatocytes both necrotic and apoptotic.

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Sequencing of the smallest Apicomplexan genome from the human pathogen Babesia microti†

Cited by 185 publications

References 76 publications

Expression, Purification, and Biological Characterization of Babesia microti Apical Membrane Antigen 1

Expression, Purification, and Biological Characterization of Babesia microti Apical Membrane Antigen 1

Extensive Shared Chemosensitivity between Malaria and Babesiosis Blood-Stage Parasites

Babesia Microti – Known and Unknown Protists

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